This project focuses on basic and applied research on human retroviruses, HIV-1 and HTLV-I. It covers three broad areas--I) basic research studying the regulated expression of HIV-1; II) basic research on cellular transformation events as related to HTLV-I; and III) applied research towards developing HIV-1-based vectors and designing molecular ribozymes targeted against HIV-1. Some notable scientific findings from our research program in 1997-1998 include: 1) the demonstration that Tat binds a histone acetylase and affects transcription of integrated LTR-promoters; 2) evidence that Tat can influence shut-off host cell protein synthesis by binding to EF-1d; 3) evidence that extracellular Tat protein antagonize CXCR4-receptor usage; 4) generation of an attenuated HIV-1 virus using IkB-a; 5) the characterization of mitotic checkpoint proteins HsMAD1 and HsMAD2 and their interactions with HTLV-I Tax in cellular transformation; 6) demonstration of Tax effects on G1 to S cell phase transition through modulation of cyclin D-cdk and p110RB; 7) the identification of a novel selenium containing protein; and 8) the generation of infectious HIV viral particles containing a therapeutic ribozyme. In the coming year, we plan to extend our findings into each of these research areas.